Science is Our Passion

The objective of the SPHERE study is to show that selective PGx testing guided by urine metabolite concentrations will reduce the rate of drug-related adverse events (AEs) while also reducing unnecessary widespread PGx testing and related costs. Our preliminary data has shown promising results supporting the SPHERE objective.

Study Objective

To improve patient care by preventing drug-related adverse events in a simple and cost-effective way.

Just as genetics contribute to whether you are tall or short, black or blonde haired, genetics also affect how you may respond to certain medicines. Prodrugs, such as hydrocodone are activated by Cytochrome (CYP) P450 enzymes in the liver during Phase I metabolism to produce the therapeutic effect. If patient has a genetic mutation, it can lead to increased side effects or reduced therapeutic effect.

Current PGx Dilemma

90% of patients are paying for a test that delivers no benefit to their treatment.

On average, only 10% of patients receiving cytochrome P450 PGx testing are identified as abnormal metabolizers1

SPHERE Study Goal

Minimize the cost of healthcare

The SPHERE hypothesis asserts that selective PGx testing guided by urine metabolite concentrations will reduce the rate of drug-related adverse events (AEs) while also reducing unnecessary widespread PGx testing and related costs.

1 Wijnen PA, Op den Buijsch RA, Drent M, et al. Review article: The prevalence and clinical relevance of cytochrome P450 polymorphisms. Aliment Pharmacol Ther 2007;26 Suppl 2:211-9.

How the Study Works

Study Design

InSource Diagnostics is recruiting 14,000 subjects in up to 200 research sites from a multi-disciplinary representation of physicians, including Pain Management, Family Practice, Internal Medicine, Psychiatry, Addiction, and/or Rheumatology who actively prescribe the Target Drugs for durations longer than 90 days.

Who Can Participate?

To be eligible for the study, subjects must meet all of the following requirements:

  • Subject is 12 years of age or older;
  • Subject or legal representative is able and willing to provide informed consent;
  • Subject has had a Target Drug-related Adverse Events (TDRAE)* within the last 60 days or is a new patient to the treating healthcare provider's practice;
  • Subject is scheduled for, or is planned to be scheduled for, urine drug test ordered as per the treating healthcare provider's local standard of care;
  • Subject is currently receiving or the subject's treating healthcare provider is considering treatment with at least one target drug, defined as a medication that falls within one of the following classes of medications and metabolized by a cytochrome P450 pathway: 
    • Antidepressants; 
    • Benzodiazepines;
    • Opioids;
    • Muscle relaxants.

Frequently Asked Questions

What time commitment is required by patients/subjects?

There is little if any additional time commitment for the patient. In most cases the only time a patient spends is 5-10 minutes during informed consent.

What time commitment is required by the clinicians?

A clinic can expect to spend about 20 minutes per subject within the 90-day study period. About 10 minutes of the estimated time is allocated to obtaining informed consent from the patient. The remaining 10 minutes is spent updating case report forms during the subsequent visits. The actual time commitment by the Physician will vary depending on how much of the work is done by the Medical Assistant or other support staff.

What costs will be incurred?

The subjects and clinicians will incur no costs for trial participation beyond their typical costs for UDT. UDTs will be billed to the subject's insurance provider at the usual and customary rates. If the subject qualifies for a PGx test, InSource Diagnostics will cover all PGx-related costs.

Is there a compensation for participation in the SPHERE study?

No compensation will be provided to the subjects for participating in the trial. However research sites will be compensated $50 per subject for their additional time commitments necessary for the study. This fee was established by an independent appraiser, Healthcare Appraisers, Inc., that assessed the true Fair Market Valuation (FMV) for the work described above. A full copy of the FMV is available upon request.

Medications Evaluated by the SPHERE Clinical Trial

The table below lists the drugs being evaluated for the trial and the corresponding genes involved in metabolism. If the trial is successful, we hope to add additional drugs that have genetic implications

Pharmacogenetics

Pharmacogenetic Testing

Just as genetics contribute to whether you are tall or short, black-haired or blond, genetics also affect how you may respond to certain medicines. Pharmacogenetic testing is used to correlate targetable genetic-related differences to predict how certain medications may behave when taken.

How is testing done?

Just a quick swab to the inside of your mouth and you're done! Our lab extracts the specific portions of DNA responsible for drug metabolism from the swabbed cells. All other DNA is unused. Analysis of these specific segments can tell us how your genes affect the metabolism of certain drugs. It's that easy.

How does metabolic status affect prescribed medications?

Metabolic Profile Severity Physician Action Non-Prodrug Prodrug
UltraRapid Abnormal Select alternative drugs or adjust dosages Reduced drug effect at typical dosages, consider alternatives High risk of toxicity or adverse side effects
Extensive Normal NONE Normal response as per drug label
Intermediate Abnormal Prescribe with caution Increased risk of toxicity or adverse side effects Avoid other drugs that would inhibit metabolism
Poor Abnormal Select alternative drugs or adjust dosages High risk of toxicity or adverse side effects. Consider reducing starting dose Reduced drug effect at typical dosages, consider alternatives

Key: Problematic Caution Normal

Non-Prodrugs: Morphine (Kadian®), Hydromorphone (Dilaudid®) 
Prodrugs: Amitriptyline (ELAVIL®), Codeine, Oxycodone (Opana®), Tramadol (Ultram®)

 

Pharmacogenetic Information for Common Medications

  CLASS DRUG TRADE NAME GENES
CARDIOLOGY ANTIARRHYTHMICS DIGOXIN LANOXIN®, DIGITEK® ABCB1
FLECAINIDE TAMBACOR™ CYP2D6
PROPAFENONE RYTHMOL SR® CYP2D6
ANTICOAGULANTS WARFARIN COUMADIN® CYP2C9, VKORC1
ANTIDIABETICS REPAGLINIDE PRANDIN® SLC01B1
TOLBUTAMIDE ORINASE® CYP2C9
ANTIHYPERTENSIVES LOSARTAN COZAAR®, HYZAAR® CYP2C9
METOPROLOL LOPRESSOR®, TOPROL XL® CYP2D6
PLATELET AGGREGATION INHIBITORS CLOPIDOGREL PLAVIX® CYP2C19, ABCB1, CYP3A4
STATINS ATORVASTATIN LIPITOR® SLC01B1, ABCB1, CYP3A5
PRAVASTATIN PRAVACHOL® SLC01B1
ROSUVASTATIN CRESTOR® SLC01B1
SIMVASTATIN ZOCOR®, SIMCOR® SLC01B1, ABCB1, CYP3A5
THROMBOPHILIAS THROMBOPHILIA   F2, F5
PAIN MANAGEMENT ANTIDEPRESSANTS AMITRIPTYLINE ELAVIL® CYP2D6, CYP2C19
CITALOPRAM CELEXA® CYP2C19, HTR2A, GRIK4
CLOMIPRAMINE ANAFRANIL® CYP2D6, CYP2C19
DESIPRAMINE NORPRAMIN® CYP2D6
DOXEPIN SINEQUAN® CYP2D6, CYP2C19
ESCITALOPRAM LEXAPRO® CYP2C19, HTR2A
IMIPRAMINE TOFRANIL™ CYP2D6, CYP2C19
VALPROIC ACID DEPAKOTE®, STAVZOR® CYP2C9
NORTRIPTYLINE PAMELOR™ CYP2D6, ABCB1
PAROXETINE PAXIL® , PEXEVA® CYP2D6, HTR2A
TRIMIPRAMINE SURMONTIL® CYP2D6, CYP2C19
VENLAFAXINE EFFEXOR® CYP2D6
ANTIEPILEPTICS MEPHENYTOIN MESANTOIN® CYP2C19
PHENYTOIN DILANTIN® CYP2C9, ABCB1
BENZODIAZEPINES DIAZEPAM VALIUM® CYP2C19
GENERAL ANESTHETICS NITROUS OXIDE NITRONOX MTHFR
MUSCLE RELAXANTS CARISOPRODOL SOMA® CYP2C19
NSAIDs CELECOXIB CELEBREX® CYP2C9
DICLOFENAC VOLTAREN®, CATAFLAM® CYP2C9
OPIOIDS CODEINE TYLENOL® #3 CYP2D6
HYDROCODONE LORTAB® , VICODIN® CYP2D6
OXYCODONE OXYCONTIN®, PERCOCET® CYP2D6
TRAMADOL ULTRAM® CYP2D6
MENTAL HEALTH ANTIDEPRESSANTS AMITRIPTYLINE ELAVIL® CYP2D6, CYP2C19
CITALOPRAM CELEXA® CYP2C19, HTR2A, GRIK4
CLOMIPRAMINE ANAFRANIL® CYP2D6, CYP2C19
DESIPRAMINE NORPRAMIN® CYP2D6
DOXEPIN SINEQUAN® CYP2D6, CYP2C19
PAROXETINE PAXIL® , PEXEVA® CYP2D6, HTR2A
ESCITALOPRAM LEXAPRO® CYP2C19, HTR2A
IMIPRAMINE TOFRANIL™ CYP2D6, CYP2C19
NORTRIPTYLINE PAMELOR™ CYP2D6, ABCB1
TRIMIPRAMINE SURMONTIL® CYP2D6, CYP2C19
VENLAFAXINE EFFEXOR® CYP2D6
ANTIEPILEPTICS MEPHENYTOIN MESANTOIN® CYP2C19
PHENYTOIN DILANTIN® CYP2C9, ABCB1
VALPROIC ACID DEPAKOTE®, STAVZOR® CYP2C9
ANTIPSYCHOTICS ARIPIPRAZOLE ABILIFY® CYP2D6
HALOPERIDOL HALDOL® CYP2D6
OLANZAPINE ZYPREXA® HTR2A
RISPERIDONE RISPERDAL® CYP2D6, HTR2A
OTHER CHEMOTHERAPEUTICS TAMOXIFEN NOLVADEX®, SOLTAMOX® CYP2D6
CORTICOSTEROIDS PREDNISONE DELTASONE®, STERAPRED® ABCB1
HIV/AIDS EFAVIRENZ SUSTIVA® CYP3A5, ABCB1
NELFINAVIR VIRACEPT® ABCB1
NEVIRAPINE VIRAMUNE® CYP3A5, ABCB1
IMMUNOSUPPRESSANTS CYCLOSPORINE SANDIMMUNE® CYP3A5, ABCB1
MERCAPTOPURINE PURINETHOL® MTHFR
SIROLIMUS RAPAMUNE® CYP3A5
TACROLIMUS PROGRAF® CYP3A5
PROTON PUMP INHIBITORS LANSOPRAZOLE PREVACID® CYP2C19
OMEPRAZOLE PRILOSEC® CYP2C19
PANTOPRAZOLE PROTONIX® CYP2C19

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